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. 2025 Apr 23;25(1):187.
doi: 10.1186/s12890-025-03651-8.

Characterization of the Mmalton carrier's cohort within the EARCO (European Alpha- 1 Antitrypsin Research Collaboration) registry

Beatriz D Ferraz  1   2 , Maria Sucena  3 , Margarida Fonseca Cardoso  4   5 , Alice M Turner  6   7 , José María Hernández-Pérez  8 , María Torres-Duran  9   10 , Hanan Tanash  11 , Carlota Rodríguez-García  12   13 , Jens-Ulrik Jensen  14   15 , Angelo Corsico  16   17 , José Luis López-Campos  10   18 , Kenneth Chapman  19   20 , Christian F Clarenbach  21 , Joana Gomes  3 , Marc Miravitlles  22 , Beatriz Lara  23
Affiliations

Characterization of the Mmalton carrier's cohort within the EARCO (European Alpha- 1 Antitrypsin Research Collaboration) registry

Beatriz D Ferraz et al. BMC Pulm Med. .

Abstract

Introduction: The PI*Mmalton variant is a rare form of alpha-1-antitrypsin (AAT) deficiency, caused by a mutation in the SERPINA1 gene and associated with reduced AAT levels. Its clinical significance remains uncertain due to the limited number of reported cases.

Methods: This study characterizes PI*Mmalton carriers within the EARCO (European Alpha-1 Antitrypsin Research Collaboration) registry and compares them with PI*ZZ individuals. Patients were categorized into moderate PI*Mmalton (combined with PI*S or PI*I) and severe PI*Mmalton (combined with PI*Z, PI*Mmalton, PI*MProcida, or PI*MHerleen). Demographic data, lung function, respiratory symptoms, disease prevalence, and augmentation therapy use were analyzed.

Results: Among 2074 individuals, 59 (2.8%) carried a PI*Mmalton allele. Severe PI*Mmalton patients exhibited lung function impairment comparable to PI*ZZ individuals, with a significantly lower FEV₁/FVC ratio (55.9% vs. 57.6%) and similar AAT levels (~ 25 mg/dL). Moderate PI*Mmalton patients had better lung function and higher AAT levels (median 54 mg/dL). Emphysema was more prevalent in severe PI*Mmalton (54.5%) and PI*ZZ (61.2%) than in moderate PI*Mmalton (34.6%). Augmentation therapy use was highest in severe PI*Mmalton (45.2%). Liver disease prevalence was comparable across groups.

Conclusion: Severe PI*Mmalton patients exhibit clinical and functional similarities to PI*ZZ individuals, suggesting a comparable disease burden. Moderate PI*Mmalton patients, however, show milder impairment. These findings reinforce the need for genotype-specific management strategies and suggest that PI*Mmalton carriers, particularly those with severe variants, should be considered in future clinical trials.

Keywords: Alpha-1 antitrypsin; Lung disease; PI*Mmalton; Registries.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study protocol received central ethics approval by the research ethics committee of the Vall d’Hebron University Hospital of Barcelona, Spain (PR(AG)480/2018) and was subsequently approved by all participating centres. All participants provided written informed consent. Consent for publication: Not applicable. Competing interests: Beatriz D Ferraz has received speaker fees and support for attending meetings from CSL Behring. Maria Sucena has received consulting fees from Bial, GlaxoSmithKline, CSL Behring and Grifols, speaker fees from AstraZeneca, Bial, CSL Behring, Grifols, GlaxoSmithKline and Novartis, support for attending meetings from Bial, CSL Behring, Grifols and Medinfar, honoraria for participation on advisory board from Bial and CSL Behring.Alice M Turner has received either grants or speaker fees from AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, CSL Behring, Takeda, Vertex, Alpha 1 Foundation and Grifols. José María Hernández- Pérez has received speaker fees from Bial, CSL Behring and GlaxoSmithKline, and support for attending meetings from Grifols and CSL Behring. María Torres-Durán has received either grants or speaker fees from Grifols, IISCIII (Instituto de Investigación Sanitaria Carlos III), IISGS (Instituo de Investigación Sanitaria Galicia Sur), CSL Behring and GlaxoSmithKline, and support for attending meeting from FAES, Bial and Chiesi. Hanan Tanash has received speaker fees from AstraZeneca, GlaxoSmithKline, Boehringer Ingelheim, Chiesi and Grifols. Carlota Rodríguez-García has received speaker fees from GlaxoSmithKline, Bial, AstraZeneca and CSL Behring, and support for attending meetings from Chiesi and Grifols.Angelo Corsico has received consulting fees from GlaxoSmithKline, Grifols, CSL Behring, Zambon and Bruschettini and support for attending meetings from AstraZeneca and Chiesi. José Luis López-Campos has received honoraria during the last 3 years for lecturing, scientific advice, participation in clinical studies or writing for publications for (alphabetical order): AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, CSL Behring, Faes, Gebro Pharma, GlaxoSmithKline, Grifols, Menarini and Zambon.Kenneth Chapman has received grant or contracts from BMS, Bellus, AstraZeneca, GlaxoSmithKline, Sanofi, Regeneron, Takeda and Novartis, consulting fees from AstraZeneca, GSK, Inhibrix, Mereo, Regeneron, Sanofi and Takeda; speaking fees from Valeo, Sanofi, Novartis, GSK and Takeda. Christian F Clarenbach has received consulting fees from AstraZeneca, Boehringer Ingelheim, CSL Behring, Daiichi Synkyo, GlaxoSmithKline, Novartis, Sanofi, OM Pharma, MSD, Grifols and Vifor and speaking fees from AstraZeneca, Boehringer Ingelheim, CSL Behring, Daiichi Synkyo, GlaxoSmithKline, Novartis, Sanofi, OM Pharma, MSD and Grifols, Vifor.Joana Gomes has received speaker fees from AstraZeneca, GlaxoSmithKline, CSL Behring and Tecnimede and support for attending meetings from Tecnimede. Marc Miravitlles has received grants or contracts from Grifols speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Bial, GlaxoSmithKline, Menarini, Kamada, Takeda, Zambon, CSL Behring, Specialty Therapeutics, Janssen, Grifols, Zambon, Tabuk Pharmaceuticals, Glenmark Pharmaceuticals, Sanofi/Regeneron and Novartis, support for attending meetings from Boehringer Ingelheim, Menarini, Chiesi, Bial, CSL Behring and Grifols and consulting fees AstraZeneca, Atriva Therapeutics, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, CSL Behring, Inhibrx, Ferrer, Menarini, Mereo Biopharma, Spin Therapeutics, Specialty Therapeutics, BridgeBio, AstraZeneca, Atriva Therapeutics, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, CSL Behring, Inhibrx, Ferrer, Menarini, Mereo Biopharma, Spin Therapeutics, Specialty Therapeutics, BridgeBio, Palobiofarma SL, Takeda, Novartis, Beam therapeutics, Novo Nordisk, Sanofi/Regeneron, Zambon, Zentiva and Grifols. The remaining authors report no competing interests.

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